Cited by 248Paraquat toxicity studies and treatmentsCoenzyme Q10 studies and effectsParkinson's Disease Mechanisms and Treatments

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Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

McCarthy, S., Somayajulu, M., Sikorska, M., Borowy-Borowski, H., Pandey, S.·2004·Toxicology and Applied Pharmacology

DOI 10.1016/j.taap.2004.04.019

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Abstract

Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q10 (CoQ10) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins.

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Authors: McCarthy, S., Somayajulu, M., Sikorska, M., Borowy-Borowski, H., & Pandey, S.
Affiliations: University of Windsor (CA)
National Research Council Canada (CA)
Corresponding author: Pandey, S.
ORCID: Somayajulu, M.
Pandey, S.
Venue: Toxicology and Applied Pharmacology
Publisher: Elsevier BV
Published: 2004-11
Volume: 201
Issue: 1
Pages: 21-31
ISSN: 0041-008X (ISSN-L)
DOI: 10.1016/j.taap.2004.04.019
OpenAlex: W1975416756
Cited by: 248
References: 34
Citations by year: 2026: 3 · 2025: 10 · 2024: 4 · 2023: 8 · 2022: 12 · 2021: 16 · 2020: 10 · 2019: 18 · 2018: 9 · 2017: 16 · 2016: 13 · 2015: 9 · 2014: 8 · 2013: 10 · 2012: 13
FWCI: 10.74
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Toxicology and Applied Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Paraquat toxicity studies and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: paraquat, oxidative stress, neuronal cell death, apoptosis, coenzyme Q10, neuroprotection, reactive oxygen species, mitochondrial depolarization, mitochondrial membrane potential, neurodegenerative diseases, herbicide neurotoxicity, SH-SY5Y cells, DNA fragmentation
MeSH terms: Cells, Cultured, Coenzymes, Herbicides, Humans, Mitochondria, Neuroblastoma, Neurons, Paraquat, Ubiquinone, Lipid Peroxidation, Apoptosis, Oxidative Stress, Neurotoxicity Syndromes, Comet Assay

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Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

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